Intragastric space fillers and methods of manufacturing including in vitro testing

ABSTRACT

An in vitro testing process for simulating conditions of a stomach, comprising, in combination: providing an intragastric device to an acetone bath; inducing swelling of the intragastric device; exacerbating weak spots in the intragastric device; observing the results; and estimating the results of an in vivo study. Improvements to an intragastric space filler to reduce failure at a balloon to shaft area including an adhesive fillet, washers, a balloon cuff and collar, a molded in balloon fillet, and a one-piece molded balloon assembly.

RELATED APPLICATIONS

This application claims the full Paris Convention benefit of andpriority to U.S. Provisional Patent Application Ser. No. 61/166,675,filed on Apr. 3, 2009, the contents of which are incorporated byreference herein in its entirety, as if fully set forth herein.

BACKGROUND

This disclosure relates to implantable intragastric devices and systemsand methods of in vitro testing of the same. More specifically, thisdisclosure relates to improvements to inflatable intragastric spacefiller devices to prevent undesired rupture and leakage.

SUMMARY

According to embodiments, disclosed is a process for manufacturing anintragastric device, comprising, in combination: providing a balloonhaving a body, a cuff extending from the body, and a collar at an end ofthe cuff; providing a shaft through the cuff and the collar of theballoon; folding the cuff on itself within the body of the balloon,whereby the cuff is brought to the body of the balloon and whereby thecuff forms overlapping surfaces and a folded inner surface; adhering theoverlapping surfaces of the cuff to each other at a balloon-to-ballooninterface; adhering the folded inner surface to the shaft at aballoon-to-shaft interface. A product may be produced thereby.

The overlapping surfaces of the cuff may be adhered to each other with asilicone-based adhesive. The adhesive may have a hardness about the sameas the hardness of the balloon. The folded inner surface may be adheredto the shaft with a silicone-based adhesive. The adhesive may have ahardness less than the hardness of the shaft.

According to embodiments, disclosed is an improved process formanufacturing intragastric space fillers, which comprises, incombination: providing the intragastric device having a balloon and ashaft extending through the balloon, the shaft fixed to the balloon,wherein the balloon and the shaft form a balloon-to-shaft transitionwhere an exposed surface portion of the balloon meets with an exposedsurface portion of the shaft; providing a surface fillet across at leastthe balloon-to-shaft transition. A product may be produced thereby.

The surface fillet may be a sheet bonded by an adhesive. The sheet mayform a washer concentric with the shaft. The surface fillet may be anadhesive. The surface fillet may be silicone-based. The surface filletmay have a hardness between a hardness of the shaft and a hardness ofthe balloon. The surface fillet may reduce stress concentrations nearthe transition section to facilitate a smoother transition from balloonto shaft. The process may further comprise: providing a second surfacefillet across at least a second balloon-to-shaft transition.

According to embodiments, disclosed is a kit, comprising, incombination: a shaft; a balloon having a body and two cuffs, each with acollar at an end thereof, the cuffs configured to receive the shaftthrough the two cuffs and the body of the balloon while in an assembledstate, wherein the shaft and balloon form at least one balloon-to-shafttransition where an exposed surface portion of the balloon meets with anexposed surface portion of the shaft while in the assembled state; asurface fillet configured to be placed across the balloon-to-shafttransition while in the assembled state, wherein the surface filletreduces stress concentrations near the balloon-to-shaft transition tofacilitate a smoother transition from balloon to shaft. The shaft, andthe surface fillet may be in the assembled state.

According to embodiments, disclosed is an intragastric device,comprising, in combination: a shaft having shore durometer hardness ofat most about 55A; a balloon having shore durometer hardness of at leastabout 20A and comprising a body, a cuff extending from the body, and acollar at an end of the cuff; a surface fillet across the exposedsurface portion of the balloon and the exposed surface portion of theshaft at a balloon-to-shaft transition, the surface fillet having ahardness between the hardness of the shaft and the hardness of theballoon.

The surface fillet may be a sheet bonded by an adhesive. The sheet mayform a washer concentric with the shaft. The surface fillet may be anadhesive.

According to embodiments, disclosed is an intragastric device,comprising, in combination: a shaft; a balloon comprising a body, a cuffextending from the body, and a collar at an end of the cuff; wherein aninterior portion of the body has an inner fillet having a thicknessgreater than a thickness of an equator of the balloon and configured totransition an interior wall of the balloon to at least one of the shaftand the cuff when folded within the body of the balloon.

According to embodiments, disclosed is an in vitro testing process foraccelerated simulation of conditions in a stomach, in combination:providing an intragastric device to an acetone bath; inducing swellingof the intragastric device; exacerbating weak spots in the intragastricdevice.

The process may further comprise observing the results and estimatingthe results of an in vivo study. The swelling may be induced inproportion to the permeability of the intragastric device. The acetonebath may contain at least about 95% acetone by volume. The acetone bathmay be provided at room temperature. The intragastric device and theacetone bath may be maintained in a sealed environment. A time tofailure of the intragastric device in the in vitro testing process maybe linearly related to a projected time to failure in an in vivo study.

According to embodiments, disclosed is an in vitro testing process foraccelerated simulation of conditions in a stomach, comprising, incombination: providing an intragastric device to a hydrochloric bath ofpH between about 1.0 and about 1.5, heated to between about 50° C. andabout 60° C.; exacerbating weak spots in the intragastric device.

The process may further comprise: observing the results and estimatingthe results of an in vivo study.

According to embodiments, disclosed is a process for manufacturing aballoon of an intragastric device, comprising, in combination:subjecting materials for the balloon to a heated environment, wherebybetween about 85% and about 95% of a target property for the balloon isachieved by partial cross-linking; removing the balloon from the heatedenvironment, whereby additional cross-linking is achieved and driven byresidual heat retained from the heated environment; and subjecting theballoon to radiation-based sterilization, whereby about 100% of thetarget property is achieved. A product may be produced thereby.

The target property may be resistance to failure when subjected to amechanical stress. The target property may be resistance to failure whensubjected to a mechanical stress. The mechanical stress may be torque.The mechanical stress may be elongation. The target property may betensile strength. The target property may be resistance to ingress andegress across walls of the balloon. The materials for the balloon may besilicone-based. The radiation-based sterilization may be gammasterilization.

DRAWINGS

The above-mentioned features and objects of the present disclosure willbecome more apparent with reference to the following description takenin conjunction with the accompanying drawings wherein like referencenumerals denote like elements and in which:

FIG. 1 shows a perspective view of an intragastric space filler;

FIG. 2 shows a front view of a balloon;

FIG. 3 shows a perspective view of a balloon;

FIG. 4 shows a side view of a balloon;

FIG. 5 shows a sectional view of a balloon;

FIG. 6 shows a front view of a balloon;

FIG. 7 shows a perspective view of a balloon;

FIG. 8 shows a side view of a balloon;

FIG. 9 shows a sectional view of a balloon;

FIG. 10 shows a sectional view of a balloon and shaft;

FIG. 11 shows a front view of a balloon;

FIG. 12 shows a perspective view of a balloon;

FIG. 13 shows a side view of a balloon;

FIG. 14 shows a sectional view of a balloon;

FIG. 15 shows a sectional view of a balloon;

FIG. 16 shows a sectional view of a balloon and shaft;

FIG. 17 shows a sectional view of a balloon and shaft;

FIG. 18 shows a side view of an outer fillet;

FIG. 19 shows a sectional view of an outer fillet;

FIG. 20 shows a perspective view of an outer fillet approaching anintragastric space filler;

FIG. 21 shows a perspective view of an outer fillet on an intragastricspace filler;

FIG. 22 shows a sectional view of an outer fillet approaching anintragastric space filler;

FIG. 23 shows a sectional view of an outer fillet on an intragastricspace filler;

FIG. 24 shows a front view of a balloon;

FIG. 25 shows a perspective view of a balloon;

FIG. 26 shows a side view of a balloon;

FIG. 27 shows a sectional view of a balloon;

FIG. 28 shows a front view of a one-piece intragastric space filler;

FIG. 29 shows a perspective view of a one-piece intragastric spacefiller;

FIG. 30 shows a side view of a one-piece intragastric space filler;

FIG. 31 shows a sectional view of a one-piece intragastric space filler;

FIG. 32 shows a sectional view of a one-piece intragastric space filler;

FIG. 33 shows a graph having data plots and a fitted line plot ofresults of an embodiment of the present disclosure comparing a time tofailure of an intragastric space filler in an in vitro acetone bath(x-axis in hours) and a time to failure of an embodiment of anintragastric space filler for in vivo clinical trials (y-axis in days);and

FIG. 34 shows a sample chart with curing parameters.

DETAILED DESCRIPTION

The inventors of the present disclosure have observed late stagedeflations with inflated intragastric balloon devices used in clinicaltrials. The deflations indicate certain wear-out mechanisms—inparticular, in the area between balloon-to-shaft (BTS) bonds. During invivo tests, these manifest as balloon deflations after months within thestomach.

According to embodiments, and as shown in FIG. 1, intragastric device 10is a medical device configured to be emplaced within a gastric cavity ofa patient for a duration of time. Intragastric device 10 may includeshaft 20 with at least one balloon 30 disposed thereon. Shaft 20 mayextend through one or more balloons 30. Shaft 20 may provide structure,interfacing for implant or explant, or components for inflation ordeflation of one or more balloons 30.

According to embodiments, balloon 30 is any expandable, space fillingcomponent. Balloon 30 may have any variety of geometries and shapes. Asshown in FIGS. 2, 3, 4, and 5, balloon 30 may include body 40, with atleast one cuff 50 extending from body 40 for interfacing with othercomponents, such as shaft 20 extending through balloon 30. Collar 60 maybe provided at an end of cuff 50. Collar 60 may be thinner or thickerthan cuff 50 or be tapered, scalloped, rounded, cornered, etc. Balloon30 may be an open or closed balloon. Balloon 30 and parts thereof mayhave an inner surface and outer surface.

According to embodiments, cuff 50 of balloon 30 may be folded to withinbody 40 of balloon 30, as shown in FIGS. 6, 7, 8, 9, and 10. In such aposition, at least a portion of cuff 50 may be configured to interfacewith shaft 20. As shown in FIG. 10, balloon-to-shaft (BTS) interface 70is defined as the areas at which balloon 30 and shaft 20 are bondedtogether. For example, BTS interface 70 may be where cuff 50 is bondedto shaft 20. According to embodiments, BTS interface 70 may be disposedwithin body 40 of balloon 30. At BTS interface 70, at least one adhesivemay be provided or at least one of balloon 30 and shaft 20 may bemodified so as to form a fixation of balloon 30 relative to shaft 20.

According to embodiments, as shaft 20 extends through balloon 30,balloon-to-shaft (BTS) transition 90 is defined as one or more meetingplaces relative to an external (exposed) portion of balloon 30 and anexternal (exposed) portion of shaft 20. For example, BTS transition 90may be the point at which balloon 30 and shaft 20 meet to begin BTSinterface 70.

According to embodiments, intragastric device 10 with at least oneballoon 30 may be configured for use as an implantable device within agastric cavity. Where implant is temporary, intragastric device 10 mustbe explanted after some period of time. Durability and longevity ofintragastric device 10 may be defined, at least in part, bycharacteristics of balloon 30. Balloon 30 may be subjected to harshgastric environments for an extended amount of time. Accordingly, thematerials and manufacturing methods of the materials are keycontributors as to balloon integrity and longevity.

According to embodiments, intragastric device 10 may experience rupture,tearing, wear-out, degradation, or leakage of a balloon at or near BTSinterface 70 or BTS transition 90. According to embodiments, variousimprovements to embodiments of intragastric space fillers are disclosedherein. Such improvements apply to devices as disclosed herein, todevices as incorporated by reference, and to devices known in the art,as artisans will appreciate.

According to embodiments, accelerated in vitro models for siliconecreep/stress relaxation failure are disclosed. According to embodiments,said in vitro models closely approximate the results observed during invivo testing. Thereby, said models provide a standard by whichintragastric devices may be tested for durability and performance, wherethe results project a hypothetical in vivo experience similar to the invitro results.

In order to identify mitigations in a rapid manner for the observedwear-out mechanism, an accelerated in vitro wear-out model was developedand several engineering solutions identified. Multiple environmentaltests were developed in an attempt to accelerate the in vitro testingwhile re-creating the observed in vivo wear-out mechanisms. One testinvolved a low pH (1.0-1.5) heated bath and the other used an acetonebath at ambient temperature. As part of testing, multiple configurationsof a balloon subassembly with process enhancements were subjected to theenvironmental tests. According to embodiments, the Acetone bathreproduced seemingly identical deflation modes to those observed in thein vivo clinical trials.

According to embodiments, a heated low ph (1.0-1.5) hydrochloric bathcreates an accelerated (through increased heat and ambient temperatureadjusted to 37° C.) in vitro stomach environment (low pH). The testmethod may exacerbate any weak spots in the balloon assembly in anaccelerated fashion.

According to embodiments, hydrochloric bath tests did produce failuresin intragastric space fillers, but they were not uniformly produced inthe BTS area as seen in the clinical units. The time to failure rangedfrom 15-112 hours after the start of testing. All failures were locatedin the equator region of the balloon. The heated low pH bath test servesas an acute failure test of overall balloon integrity at a moderatetemperature (50-60° C.).

According to embodiments, an acetone bath creates an accelerated invitro stomach environment. Acetone, as a solvent, induced swelling (upto 180% of the original size, from Dow Corning Form #45-0113D-01,Silicone Rubber: Fluid Resistance Guide (2005). The induced stressexacerbates any weak spots in a balloon in an accelerated fashion in aneffort to recreate the deflations found during in vivo clinical trials.

According to embodiments, the volume of solvent used for each testsample remains constant for solvent concentration consistency. The bathmay contain between about 95% to about 100% acetone by volume. The testmay be performed at room temperature, with a test sample and bathcontents in a sealed, air-tight container.

According to embodiments, balloon samples soaked in acetone tend tobecome stiffer, whereby they achieve reduced elongation and tensileabilities due to a higher modulus. The stress relaxation becomes slower,yielding lower creep rates. Additionally, the balloon is swelling(osmosis of acetone into the balloon cavity & vice versa for saline &methylene blue expelling through the open pores, confirmed by blue tintin acetone bath during prolonged testing) and building up volume,inducing more stress as test time increases. The stress is dependent onthe size of the balloon (larger balloon means larger stresses) and itsporosity and permeability.

Baseline and multiple product enhancements and configurations weresubjected to the acetone bath test. 40 of 42 failed at the bonding areabetween the shaft and balloon, one unit failed at the equator, and otherenhanced units did not fail. This test method did successfully recreatethe failures in a repeatable manner (all standard clinical configurationand enhancement units failed in the bonded region between the shaft andballoon).

FIG. 33 shows a graph having data plots and a fitted line plot ofresults of an embodiment of the present disclosure comparing a time tofailure of an embodiment of an intragastric space filler in acetone(x-axis in hours) with a time to failure of an embodiment of anintragastric space filler in clinical trials (y-axis in days). Thecorrelation between in vitro acetone wear-out models and in vivo modelsfor intragastric balloons is shown. Data points are provided, as well asa fitted plot line, demonstrating the essentially linear relationshipbetween in vitro and in vivo models (R and R² values of 100.0%).

According to embodiments, balloon-to-shaft (BTS) regions are subjectedto considerable radial expansion when removing balloon 30 from a mandrelafter a molding process. Because the widest portion of the mandrel mustpass through cuff 50, expansion thereof may be high (exceeding 500% insome cases). This may leave balloon 30 with permanent stress marks,which may manifest as device failure in late stage operation. Studieswere conducted comparing BTS regions near each of (1) cuffs throughwhich mandrels were removed and (2) cuffs unexpanded during the moldingprocess. BTS regions subjected to expansion during mandrel removalshowed statistically lower tensile abilities by in vivo and in vitrotesting.

According to embodiments, an improved configuration for intragastricdevice 10 is disclosed. According to embodiments, as shown in FIGS. 11,12, 13, 14, and 15, cuff 50 may be folded upon itself within body 40 ofballoon 30, whereby cuff 50 forms overlapping surfaces. As shown inFIGS. 14 and 15, cuff 50 may form bi-layered cuff 50, wherebyballoon-to-balloon (BTB) interface 80 is created. Cuff 50 may be bondedto itself at BTB interface 80, for example, with adhesive. The bondingmay occur by applying adhesive to an outer portion of the cuff 50, whichbecomes folded onto itself to form BTB interface 80.

According to embodiments, folding cuff 50 causes collar 60 to be broughtto body 40. For example, as shown in FIGS. 11, 12, 13, 14, and 15,collar 60 may be flush with, in contact with, or otherwise brought intoclose proximity to body 40. Collar 60 may have a geometry that providesa natural fillet between body 40 and shaft 20.

According to embodiments, as shown in FIGS. 16 and 17, shaft 20 mayextend through balloon 30 including folded bi-layered cuff 50. Accordingto embodiments, bi-layered cuff 50 includes a folded inner surfacedefined as the portion of cuff 50 facing shaft 20. In such aconfiguration, BTS interface 70 is defined as between the folded innersurface of cuff 50 and the portion of shaft 20 contacted thereby.According to embodiments, balloon 30 may be bonded to shaft 20 at BTSinterface 70.

According to embodiments, at least one of cuff 50 and collar 60, ratherthan body 40, may form BTS transition 90 to shaft 20, as shown in FIGS.16 and 17. Where body 40 is prevented from being directly bonded toshaft 20, bi-layered cuff 50 and adhesive layers may distribute stressconcentrations from shaft 20 to body 40. Thicker layers of flexiblematerials may thereby be provided between body 40 and shaft 20.

According to embodiments, balloons 30 with bi-layered cuffs 50 showedimproved performance relative to balloons 30 with single-layered cuffs50 during an in vitro study in an accelerated in vitro test environmentutilizing an acetone bath (average time to failure improved from 7.57hours with single-layer to 74.57 hours with bi-layer).

According to embodiments, one or more BTS transitions 90 at one or moreends of balloon 30 may be provided with enhanced stress distribution byan improved mechanical joint reinforcement. For example, surface fillet100 may be provided, as shown in FIGS. 18 and 19. Surface fillet 100 maybe any structure configured to be placed at BTS transition 90 across atleast an exposed surface of balloon 30 and an exposed surface of shaft20. Surface fillet 100 may be a sheet in the form of a washer and beconfigured to be placed concentric with shaft 20. Surface fillet 100 maybe integrated into balloon 30 or shaft 20 at a component level.

According to embodiments, surface fillet 100 may be flexible. Forexample, surface fillet 100 may be silicone-based. According toembodiments, surface fillet 100 has a hardness (durometer) less thanthat of shaft 20. For example, surface fillet 100 may have a hardnessbetween the hardness of shaft 20 and the hardness of the balloon 30, tomore evenly distribute and reduce stress concentrations transferredthere between.

According to embodiments, a process is disclosed, comprising adding(e.g., bonded with adhesive) surface fillet 100 to BTS transition 90.For example, FIGS. 20 and 22 show surface fillet 100 approachingintragastric device 100. FIGS. 21 and 23 show surface fillet 100 bondedto intragastric device 100.

According to embodiments, intragastric space fillers with washers assurface fillets 100 showed improvement over those without washers duringan in vitro study in an accelerated in vitro test environment utilizingan acetone bath (average time to failure improved from 7.57 hourswithout washers to 21.18 hours with washer).

According to embodiments, surface fillet 100 is an adhesive. Forexample, surface fillet 100 may be provided to BTS transition 90 inliquid form. Subsequently, surface fillet 100 may cure, dry, orotherwise resolve to a final form. Surface fillet 100 in its final formmay have a hardness (durometer) less than that of shaft 20. The adhesivemay be silicone-based.

According to embodiments, surface fillet 100 as an adhesive is providedin a process. The process involves adding more adhesive (e.g., siliconematerial) in the region of BTS transition 90 to help transition balloon30 to shaft 20 as a bond (mechanical joint) in a smoother fashion(reduce stress concentration). Surface fillet 100 may be the same as ordifferent from an adhesive provided at BTB interface 80.

Providing an adhesive surface fillet 100 showed improvement overstandard balloon units during an in vitro study in an accelerated invitro test environment utilizing an acetone bath (average time tofailure improved from 7.57 hours without adhesive surface fillet to13.25 hours with adhesive surface fillet).

According to embodiments, balloon 30 may include inner fillet 110, asshown in FIGS. 24, 25, 26, and 27. Inner fillet 110 may be molded induring formation of balloon 30 and may be provided to relieve stress onthe balloon as a molded-in stress relievers. A portion of inner fillet110 may be placed and configured to contribute to BTS interface 70. Aportion of inner fillet 110 may be placed and configured to contributeto BTB interface 80.

According to embodiments, wall thickness of balloon 30 increases fromthe equator (midpoint between cuffs 50) thereof to the region of BTStransition 90. For example, the thickness may increase from about 0.030″at the equator to about 0.032″ at or near BTS transition 90.

According to embodiments, shaft 20 of intragastric device 10 and balloon30 of intragastric device 10 have disparate hardness. Balloons 30 may beof low durometer, such as shore 20A. Balloons 30 may be of silicone andformed by a molding process. Shaft 20 may be of higher durometer, suchas shore 80A. Shaft 20 may be of silicone and formed by an extrusionprocess. Surface fillet 100 may be of silicone with durometer shore 24A.The steep transition of low to high durometer materials from 20A to 24Ato 80A may provide for an uneven stress distribution while under load.

According to embodiments, the durometer of shaft 20 may be reduced from80A to 55A (31% reduction). Thereby, stress is more evenly distributedbetween shaft 20 and balloon 30. This enhancement showed improvementover standard balloon units during an in vitro study in an acceleratedin vitro test environment utilizing an acetone bath (average time tofailure improved from 7.57 hours with 80A shaft to 41.07 hours with 55Ashaft).

According to embodiments, intragastric device 10 may be a single moldedpiece that includes shaft 20 and at least one balloon 30, as shown inFIGS. 28, 29, 30, 31, and 32. Each balloon 30 may be integrallyconnected to shaft 20 with at least one connection point, as shown inFIGS. 31 and 32. For example, each balloon 30 may be integrallyconnected to shaft 20 at one end and have another end (i.e., with cuff50 and collar 60) open for removal of a mandrel after a molding step.

A one-piece balloon assembly may be produced by a single molding step,rather than separate steps for respective components followed bycombination thereof. Thus, a one-piece balloon assembly may have reducedassembly time. Where balloons 30 remain open, cuff 50 and collar 60 maybe adhered to collar 20, for example by methods and processes disclosedherein.

A one-piece balloon assembly may have reduced stress concentrations byvirtue of reduced bond joints requiring adhesive or other attachmentsprovided. A one-piece balloon assembly may also provide reduction inassembly time by reducing the number of cuffs 50 that must be adhered toshaft 20.

According to embodiments, one or more kits may be provided containingone or more component. The components may include any of the devices orcomponents thereof according to embodiments as disclosed herein. Forexample, one or more of shaft 20, balloon 30, and surface fillet 100 maybe provided in a kit. The components of the kit may be assembledconfigured or adapted for assembly according to embodiments as disclosedherein. Accordingly, the components may be provided in an assembledstate or in an unassembled state.

According to embodiments, enhanced processes for generating balloons andother components of intragastric device 10 are disclosed. According toembodiments, components of intragastric device 10, such as balloons 30,may have at least one target property. As used herein, a target propertyis a feature of a component of intragastric device 10 that is desirableor required. A target property may be one that provides satisfactoryresistance or resilience to undesirable results, such as rupture, tear,creep, ingress, egress, or failure of intragastric device 10. Suchresults may be characterized by any effect that would be undesirable orunsafe during emplacement in, treatment of, or removal from a patient. Atarget property may be one or more of tensile strength, elasticity,porosity, etc. A target property may be one that provides satisfactoryresistance or resilience to torque, elongation, compression, harshchemical environment, etc.

During a curing cycle, materials used to form components of intragastricdevice 10 may be provided for molding. The materials may include anybiocompatible polymer, such as silicone and silicone-based materials.During a curing cycle, the polymer may undergo cross-linking. A curingcycle may include exposure of the materials to heat while in a mold.According to embodiments, the extent of exposure to heat over timedetermines the extent of cross-linking, which thereby determines whetheror to what degree the material approaches or reaches a target property.

According to embodiments, the materials may be exposed to a heatedenvironment based on curing parameters until they have achieved lessthan about 100% of the target property. As used herein, curingparameters are conditions under which curing cycle is performed (e.g.,temperature, time, etc.). For example, a curing cycle may continue untilthe materials achieve between about 80% and about 99% of the targetproperty. More specifically, a curing cycle may continue until thematerials achieve about 90% of the target property.

According to embodiments, the materials may be removed from the heatedenvironment prior to achieving about 100% of the target property. Thematerials may retain at least some residual heat, whereby they mayfurther approach, achieve, or exceed the target property.

According to embodiments, the materials may undergo a sterilizationoperation. During sterilization, the material may further approach,achieve, or exceed the target property. Sterilization may provide heator otherwise result in additional cross-linking of the material.Sterilization may include exposure to radiation (e.g., gamma rays,electron beams, X-rays, ultraviolet light, subatomic particles, etc.).For example, where a curing cycle and residual heat are insufficient toachieve about 100% of the target property, the sterilization may besufficient to do so.

According to embodiments, curing parameters may be determined based onthe target property and the material (i.e., material lot). For example,where a silicone material was used and gamma sterilization wasperformed, the material was determined to achieve between about 90% andabout 100% of its exemplary target property (i.e., torque) after beingcured to 90% of the same target property by the heated environment(i.e., at 285° C.±5° C.) and residual heat thereafter. As shown in FIG.34, a material may have a known progression toward a target propertyover time at a given temperature. Such information may often be obtainedby a materials provider. According to embodiments, as shown in FIG. 34,a certain material may asymptotically approach 30.0 points on the torquecurve. The point in time at which it reaches 90% (27.0 points on thetorque curve) may be determined, thereby yielding a curing parameter ofthe curing cycle. The curing parameters may accommodate the effect ofresidual heat after removal from the heated environment as well as theeffect of sterilization. For example, the remaining 10% of the curing(cross-linking) occurred while the materials were waiting to be removedoff the mold and during gamma sterilization.

According to embodiments, this enhancement showed improvement overstandard balloon units during an in vitro study in an accelerated invitro test environment utilizing an acetone bath (average time tofailure improved from 7.57 hours in standard units to 41.54 hours basedon an embodiment of the above method).

According to embodiments, full curing may be useful in someapplications. For example, a balloon was 100% cured within the mold byan extended cure time that exceeded the amount required to ensure that100% of the target property was achieved. Based on the chart shown inFIG. 34, a cure time of 5 minutes was used (i.e., over double the timerequired to achieve 90% of the target property). The samples showedhigher average dog bone tensile forces (5.208 lbs vs. 4.874 lbs) withincreased average elongation (1090% vs. 1078%); but the resistance tocreep was drastically lower compared to samples processed to 90% of thetarget property in the mold.

According to embodiments, this enhancement showed decreased creepresistance relative to samples processed to 90% of the target propertyin the mold during an in vitro study in an accelerated in vitro testenvironment utilizing an acetone bath (average time to failure droppedfrom 41.54 hours in 90% mold-cured units to 17.63 hours based 100%mold-cured units). Based on the test data, the extended curing sampleshave potential application in acute or low creep (with a higher tensileforce requirements) application.

Those skilled in the art will appreciate that embodiments and featuresof embodiments disclosed herein are combinable to create synergisticbenefits.

This application incorporates by reference: U.S. Pat. Pub. No.2007/0100367, published May 3, 2007; U.S. Pat. Pub. No. 2007/0100368,published May 3, 2007; U.S. Pat. Pub. No. 2007/0100369, published May 3,2007; U.S. Pat. Pub. No. 2007/0149994, published Jun. 28, 2007; U.S.Pat. Pub. No. 2008/0243071, published Oct. 2, 2008; U.S. Pat. Pub. No.2008/0319471, published Dec. 25, 2008; U.S. Pat. Pub. No. 2005/0159769,published Jul. 21, 2005; U.S. Pat. Pub. No. 2009/0048624, published Feb.19, 2009; WIPO Pub. No. WO 2007/053556, published Oct. 5, 2007; WIPOPub. No. WO 2007/053707, published Oct. 5, 2007; WIPO Pub. No. WO2007/053706, published Oct. 5, 2007; and WIPO Pub. No. WO 2007/075810,published May 7, 2007; each as if fully set forth herein in itsentirety.

While the method and agent have been described in terms of what arepresently considered to be the most practical and preferred embodiments,it is to be understood that the disclosure need not be limited to thedisclosed embodiments. It is intended to cover various modifications andsimilar arrangements included within the spirit and scope of the claims,the scope of which should be accorded the broadest interpretation so asto encompass all such modifications and similar structures. The presentdisclosure includes any and all embodiments of the following claims.

It should also be understood that a variety of changes may be madewithout departing from the essence of the invention. Such changes arealso implicitly included in the description. They still fall within thescope of this invention. It should be understood that this disclosure isintended to yield a patent covering numerous aspects of the inventionboth independently and as an overall system and in both method andapparatus modes.

Further, each of the various elements of the invention and claims mayalso be achieved in a variety of manners. This disclosure should beunderstood to encompass each such variation, be it a variation of anembodiment of any apparatus embodiment, a method or process embodiment,or even merely a variation of any element of these.

Particularly, it should be understood that as the disclosure relates toelements of the invention, the words for each element may be expressedby equivalent apparatus terms or method terms—even if only the functionor result is the same.

Such equivalent, broader, or even more generic terms should beconsidered to be encompassed in the description of each element oraction. Such terms can be substituted where desired to make explicit theimplicitly broad coverage to which this invention is entitled.

It should be understood that all actions may be expressed as a means fortaking that action or as an element which causes that action.

Similarly, each physical element disclosed should be understood toencompass a disclosure of the action which that physical elementfacilitates.

Any patents, publications, or other references mentioned in thisapplication for patent are hereby incorporated by reference. Inaddition, as to each term used it should be understood that unless itsutilization in this application is inconsistent with suchinterpretation, common dictionary definitions should be understood asincorporated for each term and all definitions, alternative terms, andsynonyms such as contained in at least one of a standard technicaldictionary recognized by artisans and the Random House Webster'sUnabridged Dictionary, latest edition are hereby incorporated byreference.

Finally, all referenced listed in the Information Disclosure Statementor other information statement filed with the application are herebyappended and hereby incorporated by reference; however, as to each ofthe above, to the extent that such information or statementsincorporated by reference might be considered inconsistent with thepatenting of this/these invention(s), such statements are expressly notto be considered as made by the applicant(s).

In this regard it should be understood that for practical reasons and soas to avoid adding potentially hundreds of claims, the applicant haspresented claims with initial dependencies only.

Support should be understood to exist to the degree required under newmatter laws—including but not limited to United States Patent Law 35 USC132 or other such laws—to permit the addition of any of the variousdependencies or other elements presented under one independent claim orconcept as dependencies or elements under any other independent claim orconcept.

To the extent that insubstantial substitutes are made, to the extentthat the applicant did not in fact draft any claim so as to literallyencompass any particular embodiment, and to the extent otherwiseapplicable, the applicant should not be understood to have in any wayintended to or actually relinquished such coverage as the applicantsimply may not have been able to anticipate all eventualities; oneskilled in the art, should not be reasonably expected to have drafted aclaim that would have literally encompassed such alternativeembodiments.

Further, the use of the transitional phrase “comprising” is used tomaintain the “open-end” claims herein, according to traditional claiminterpretation. Thus, unless the context requires otherwise, it shouldbe understood that the term “compromise” or variations such as“comprises” or “comprising”, are intended to imply the inclusion of astated element or step or group of elements or steps but not theexclusion of any other element or step or group of elements or steps.

Such terms should be interpreted in their most expansive forms so as toafford the applicant the broadest coverage legally permissible.

The invention claimed is:
 1. A process for manufacturing intragastricspace fillers, the process comprising: providing an intragastric devicehaving a balloon and a shaft extending through at least one wall of theballoon, wherein the shaft is affixed to the balloon, and wherein theballoon and the shaft form a balloon-to-shaft transition where anexposed surface portion of the balloon meets with an exposed surfaceportion of the shaft; and providing a surface fillet at or adjacent tothe balloon-to-shaft transition, wherein the surface fillet isconfigured to reduce stress concentrations near the balloon-to-shafttransition to increase failure resistance proximate to theballoon-to-shaft transition.
 2. The process of claim 1 wherein thesurface fillet comprises a sheet bonded by an adhesive at or adjacent tothe balloon-to-shaft transition.
 3. The process of claim 2 wherein thesheet forms a washer concentric with the shaft.
 4. The process of claim1 wherein the surface fillet comprises an adhesive.
 5. The process ofclaim 1 wherein the surface fillet comprises a silicone-based material.6. The process of claim 1 wherein the surface fillet has a firsthardness, the shaft has a second hardness, and the balloon has a thirdhardness, and wherein the first hardness is between the second hardnessand the third hardness.
 7. The process of claim 1 wherein the surfacefillet is a first surface fillet, and wherein the process furthercomprises providing a second surface fillet at or adjacent to a secondballoon-to-shaft transition.
 8. The process of claim 1 wherein thesurface fillet is defined by a portion of the balloon.
 9. The process ofclaim 1 wherein the wall of the balloon and the shaft are formed fromthe same material and together define the surface fillet.
 10. Theprocess of claim 1 wherein the surface fillet is defined by an adhesiveand a portion of the balloon.
 11. A method of manufacturing anintragastric space filler, the method comprising: connecting a shaft toa balloon, wherein the balloon and the shaft meet at a balloon-to-shafttransition, and wherein the shaft extends through at least a portion ofthe balloon; and forming a surface fillet proximate the balloon-to-shafttransition, wherein the surface fillet is configured to reduce stressconcentrations proximate to the balloon-to-shaft transition.
 12. Themethod of claim 11 wherein the balloon comprises a body, a cuffextending from the body, and a collar at an end of the cuff, and whereinthe method further comprises: folding the cuff on itself within the bodyof the balloon such that the collar is positioned proximate to the body;and adhering a surface of the folded cuff to the shaft at theballoon-to-shaft interface, wherein the collar defines the surfacefillet.
 13. The method of claim 11 wherein forming the surface filletcomprises integrally forming the surface fillet with the shaft.
 14. Themethod of claim 11 wherein forming the surface fillet comprisesintegrally forming the surface fillet with the balloon.
 15. The methodof claim 11 wherein connecting the shaft to the balloon comprisesmolding a single integrated piece having the shaft extending through theballoon.
 16. The method of claim 15 wherein forming the surface filletcomprises molding the surface fillet proximate the balloon-to-shafttransition as part of the single integrated piece.